Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics

Al‐Janabi, Ali; Eyre, Steve; Foulkes, Amy C.; Khan, Adnan; Dand, Nick; Burova, Ekaterina; DeSilva, Bernadette; Makrygeorgou, Areti; Davies, Emily; Smith, Catherine; Griffiths, Christopher E.M.; Morris, Andrew P.; Warren, Richard B.

doi:10.1016/j.jid.2023.01.021

Cited by 13 publications

(3 citation statements)

References 42 publications

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“…Most of our FF patients presented history and examination criteria typical for AD and PV. Similar to other reported FF cases 12,37 and a genome‐wide association study of Al‐Janabi et al., atopy, was an important risk factor, possibly indicating a higher genetic FF predisposition in patients with atopy 57 …”

Section: Discussionsupporting

confidence: 85%

Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “Flip‐Flop” phenomenon)

Müller,

Welchowski,

Schmid

et al. 2023

Allergy

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BackgroundAtopic dermatitis (AD) and psoriasis vulgaris (PV) are almost mutually exclusive diseases with different immune polarizations, mechanisms and therapeutic targets. Switches to the other disease (“Flip‐Flop” [FF] phenomenon) can occur with or without systemic treatment and are often referred to as paradoxical reactions under biological therapy.MethodsThe objective was to develop a diagnostic algorithm by combining clinical criteria of AD and PV to identify FF patients. The algorithm was prospectively validated in patients enrolled in the CK‐CARE registry in Bonn, Germany. Afterward, algorithm refinements were implemented based on machine learning.ResultsThree hundred adult Caucasian patients were included in the validation study (n = 238 with AD, n = 49 with PV, n = 13 with FF; mean age 41.2 years; n = 161 [53.7%] female). The total FF scores of the PV and AD groups differed significantly from the FF group in the validation data (p < .001). The predictive mean generalized Youden‐Index of the initial model was 78.9% [95% confidence interval 72.0%–85.6%] and the accuracy was 89.7%. Disease group‐specific sensitivity was 100% (FF), 95.0% (AD), and 61.2% (PV). The specificity was 89.2% (FF), 100% (AD), and 100% (PV), respectively.ConclusionThe FF algorithm represents the first validated tool to identify FF patients.

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Section: Discussionsupporting

confidence: 85%

Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “Flip‐Flop” phenomenon)

Müller,

Welchowski,

Schmid

et al. 2023

Allergy

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“…The genetic polymorphisms responsible for treatment response to the different available psoriasis treatment options have been identified [ 62 , 63 , 64 ], including those related to the risk of developing antidrug antibodies [ 65 ], and have been found to correspond in many cases with type I HLA molecules. At the same time, genetic susceptibility to adverse drug reactions has also been described [ 64 , 66 ]. Since a wide range of therapeutic alternatives are available for psoriatic disease, pharmacogenomic tests prior to treatment might facilitate selection of the therapy based on individual probabilities of drug response or adverse events, providing opportunities for personalized medicine.…”

Section: Resultsmentioning

confidence: 99%

Genetic and Epigenetic Mechanisms of Psoriasis

Arrom

Puig

2023

Genes

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Psoriasis is a disease involving the innate and adaptative components of the immune system, and it is triggered by environmental factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, especially in genome and epigenome-wide studies, have provided a better understanding of the genetic and epigenetic mechanisms to determine the physiopathology of psoriasis and facilitate the development of new drugs. This review intends to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.

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“…As expected and consistent with other studies, we identified an association between paradoxical eczema and previous AD and hay fever. This supports an association of genetic factors with atopy, which we previously demonstrated in a genotyped cohort with paradoxical eczema . The lack of association with asthma could indicate that certain genetic variants more commonly associated with AD and hay fever rather than asthma, such as FLG variants, play an important role in paradoxical eczema.…”

Section: Discussionmentioning

confidence: 99%

Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis

Al-Janabi,

Alabas,

Yiu

et al. 2024

JAMA Dermatol

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ImportanceBiologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown.ObjectiveTo explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema.Design, Setting, and ParticipantsThis prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022.ExposuresDuration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death.Main Outcomes and MeasuresIncidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score–weighted Cox proportional hazards regression models.ResultsOf 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78).Conclusions and RelevanceIn this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.

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Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics

Cited by 13 publications

References 42 publications

Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “Flip‐Flop” phenomenon)

Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “Flip‐Flop” phenomenon)

Genetic and Epigenetic Mechanisms of Psoriasis

Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis

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